The Angiosperm Gibberellin-GID1-DELLA Growth Regulatory Mechanism

13 Pages·2009·0.55 MB·English

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REVIEW
The Angiosperm Gibberellin-GID1-DELLA Growth Regulatory
Mechanism: How an “Inhibitor of an Inhibitor” Enables Flexible
Response to Fluctuating Environments
NicholasP.Harberd,1EricBelfield,andYukiYasumura
DepartmentofPlantSciences,UniversityofOxford,OxfordOX13RB,UnitedKingdom
Thephytohormonegibberellin(GA)haslongbeenknowntoregulatethegrowth,development,andlifecycleprogressionof
flowering plants. However, the molecular GA-GID1-DELLA mechanism that enables plants to respond to GA has only
recentlybeendiscovered.Inaddition,studiespublishedinthelastfewyearshavehighlightedpreviouslyunsuspectedroles
for the GA-GID1-DELLA mechanism in regulating growth response to environmental variables. Here, we review these
advances within a general plant biology context and speculate on the answers to some remaining questions. We also
discussthehypothesisthattheGA-GID1-DELLAmechanismenablesfloweringplantstomaintaintransientgrowtharrest,
givingthemtheflexibilitytosurviveperiodsofadversity.
INTRODUCTION thatreducetheactivityofGAbiosynthesisenzymes(Yamaguchi,
2008).
The gibberellins (GAs) are diterpenoid compounds found in
The molecular characterization of various GA response mu-
plants,fungi,andbacteria,ofwhichonlyafewactivelyregulate
tantsledtothediscoveryoftheGID1andDELLAproteins,key
plant growth (are bioactive) (see http://www.plant-hormones.
componentsofthemolecularGA-GID1-DELLAmechanismthat
info/gibberellins.htm; Figure 1A). There has been much recent
enablesplantstorespondtoGA.Here,wetracethehistoryof
progressinunderstandingoftheregulationofthebiosynthesis
thesediscoveriesanddiscussrecentdevelopmentsthatpointto
andinactivationofbioactiveGAs(reviewedinYamaguchi,2008).
afundamentalrolefortheGA-GID1-DELLAmechanisminreg-
The GAs are derived from a basic diterpenoid carboxylic acid
ulatingthegrowthresponseoffloweringplantstoenvironmental
skeleton(Figure1A).Amongfeaturescrucialtobioactivityarethe
variables.
hydroxylgrouponC3andthecarboxylgrouponC6(Figure1A),
lackofwhichcauselossofactivity.Inaddition,hydroxylationon
C2 causes inactivation and is an important mechanism for GA-OPPOSABLEPLANTGROWTHINHIBITORS
growthregulationinangiosperms(Yamaguchi,2008).Theslight
structural differences between bioactive and inactive GAs is There are several categories of GA response mutants. Initial
indicative of the tight fit of bioactive GAs in a specific pocket interestinsuchmutantswasprovokedbythepossibilitythatthey
featureoftheGAreceptor.Thishasimportantimplicationsthat mightprovidecluesastohowplantcellsperceiveandrespondto
areexploredfurtherbelow. the GA signal. For example, the phenotype of GA-insensitive
The importance of GAs to angiosperm growth regulation is dwarfmutantsisnotrestoredtonormalbyGAtreatments(Figure
exemplified by the phenotype of GA-deficient mutants. For 1B). Genetic studies of gibberellic acid-insensitive (gai; Arabi-
example, the GA-deficient Arabidopsis thaliana ga1-3 mutant dopsis), D8 (maize [Zea mays]), and Rht-B1b/Rht-D1b (wheat
lacks ent-kaurene synthetase A, an enzyme in the GA biosyn- [Triticumaestivum])mutants(Koornneefetal.,1985;Harberdand
thesispathway,andthismutantexhibitsacharacteristicsevere Freeling, 1989; Peng and Harberd, 1993; Peng et al., 1997,
dwarfphenotype.Inaddition,ga1-3mutantseeddonotgermi- 1999a)identifiedcommonproperties:thevariousmutantalleles
nate; ga1-3 mutant shoots bear leaves that are shorter and involvedactinageneticallydominantfashionandencodeactive
darker green than the wild type and flower late in long-day (altered function) mutant products that confer dwarfism and
photoperiods(andnotatallinshort-dayphotoperiods);andga1-3 reduced GA response. Further groupings of recessive (rather
mutantflowersexhibitimpairedpetalandstamendevelopment than dominant) mutations conferring GA-insensitive dwarfism
and are male sterile. All of these aspects of the GA-deficient have more recently been characterized (e.g., McGinnis et al.,
phenotype can be corrected by exogenous GA (reviewed in 2003;Sasakietal.,2003;Ueguchi-Tanakaetal.,2005).Finally,
Richardsetal.,2001).Mutantssuchasga1-3areGA-sensitive recessiveslendermutantsexhibitexaggeratedgrowth:talland
dwarf mutants (Figure 1B) that are known in a number of slim, they resemble wild-type plants treated with saturating
different plant species and typically carry recessive mutations levelsofGAandremaintallevenwhenGAdeficient(e.g.,Potts
etal.,1985;Figure1B).
[email protected]. Studies of some of the above categories of mutant enabled
www.plantcell.org/cgi/doi/10.1105/tpc.109.066969 formal genetic definition of the mechanism via which GA
ThePlantCellPreview,www.aspb.orgã2009AmericanSocietyofPlantBiologists 1of12
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Figure1. GAStructureandResponseMutantCategories.
(A)ThestructureofabioactiveGA(GA ),showingcarboxylic(C6)andhydroxyl(C3)groupsthatareessentialforbiologicalactivity,andtheC2site,
4
hydroxylationofwhichabolishesbiologicalactivity.
(B)SchematicrepresentationofplantsinGA-relatedmutantcategories.Normal(wildtype)plantsrespondtoexogenousGA(+GA)byincreasedgrowth.
GA-sensitivedwarfmutantsareGA-deficient(–GA)andgrowinresponsetoexogenousGA.GA-insensitivedwarfmutantsdonotgrowinresponseto
exogenousGA.Finally,slendermutantgrowthmimicsthatofGA-treatednormalplants,evenwhenadditionalmutationsorchemicalgrowthretardants
causeGAdeficiency.
promotesgrowth,longbeforethemolecularbasisofthismech- MOLECULARDISCOVERYOFGA-OPPOSABLEPLANT
anism was apparent. First, analyses of pea (Pisum sativum) GROWTHINHIBITORS:THEDELLAPROTEINS
slender mutants led to the proposal that GA works as an
DiscoveryofthemolecularidentityoftheendogenousplantGA-
“inhibitorofaninhibitor”(Brian,1957).Thisproposalwasbased
opposablegrowthinhibitoryfactorresultedfromthemolecular
ontheobservationthatslendermutantsgrowtallirrespectiveof
cloningofgenesencodingwhatarenowknownastheDELLA
GAcontent(e.g.,Pottsetal.,1985).Accordingtotheinhibitorof
proteins (or DELLAs), beginning with GAI. The Arabidopsis gai
aninhibitorhypothesis,plantscontainanendogenousfactorthat
mutationconfersdominant,GA-insensitivedwarfism(Koornneef
inhibits growth, and GA promotes growth by overcoming this
etal.,1985;PengandHarberd,1993).Aninsertionalmutagen-
factor.Lackoftheendogenousgrowth-inhibitingfactorinslen-
esisapproachenabledthemolecularcloningofgaiviaisolation
dermutantscausesthemtogrowtallevenwhenGAdeficient.
Second, genetic analysis of GA-insensitive maize dwarfing ofaDstransposoninactivatedallele(gai-t6;Pengetal.,1997;
mutations led to an elaboration of the inhibitor of an inhibitor Figure 2A). Initial analysis of the amino acid sequence of GAI
hypothesis.Accordingtothiselaboration,dominantGA-insensitive gave little insight into how this protein might regulate GA re-
dwarfingmutationsconfermutantformsofthegrowth-inhibiting sponse.However,approximatelytwo-thirdsoftheGAImolecule
factorthatretainthecapacitytoinhibitgrowthbuthavelostthe (attheC-terminalend)wasfoundtoberelatedinsequencetothe
capacity to be overcome by GA (Harberd and Freeling, 1989). transcriptional regulator SCARECROW (SCR), suggesting that
Thus, the recessive slender versus dominant GA-insensitive GAImightalsobeatranscriptionalregulator(Pengetal.,1997).
dwarfmutantscould beseen asopposingmutational faces of MoreintriguingfindingscamefromthecomparisonoftheDNA
the same coin: alternative loss-of-function or altered function sequencesoftheGAIandmutantgaialleles.Thiscomparison
outcomesofmutationalchangetoanendogenousplantgrowth showedthatthegaiopenreadingframecarriesasmallin-frame
inhibitoryfactorwhosemolecularidentityremainedunknown. deletionmutationandthusencodesanalteredproduct,amutant
As described below, molecular identification of the genes gaiproteinthatlacksa17–aminoacidsegment(nowknownas
affected in GA-insensitive dwarf and slender mutants enabled theDELLAdomain,namedafteritsfirstfiveaminoacids;Peng
thediscoveryofthreeofthemajorcomponentsofwhatisnow etal.,1997;Figure2A).Thisfindingwasparticularlysignificant
known as the GA-GID1-DELLA mechanism of GA response becauseitidentifiedthemolecularbasisofthealteredfunction
regulation:theDELLAgrowthinhibitors;theF-boxproteincom- previouslyascribedtotheproductsofdominantGA-insensitive
ponent of an E3 ubiquitin ligase that specifically targets the dwarfingalleles.ItisthelackofafunctionalDELLAdomainingai
DELLAsfordestructionintheproteasomeinresponsetoGA;and that causes the reduced GA response of gai mutant plants.
theGID1GAreceptor. Further experiments showed that the gai-t6 (loss-of-function)
GrowthRegulationbyGA-GID1-DELLA 3of12
Figure2. Wild-TypeandMutantDELLAs.
(A) The Arabidopsis mutant gai allele confers dominant GA-insensitive dwarfism and was derived from the wild-type allele (GAI) via irradiation
mutagenesis(seeKoornneefetal.,1985;Pengetal.,1997).gaiencodesamutantgaiproteinthatlackstheDELLAdomain(purplesectionintheGAI
protein).ItisthelackoftheDELLAdomainthatcausesthealteredfunctionofgai,makingitaconstitutivegrowthinhibitorwhoseactivityisnotopposed
byGA.SubsequentDsinsertionmutagenesisexperimentsyieldedthegai-t6allele.ThisknockoutalleledoesnotencodeafunctionalGAI(orgai)protein
andconfersatall,slender(PAC-resistant)phenotype.
(B)ThemutantmaizeD8-1,D8-2023,andwheatRht-B1bproteinsconferdominantGA-insensitivedwarfism.Themaizeandwheatgenomesencode
DELLAproteins(d8andRht-B1a,respectively).MaizemutantallelesencodemutantD8-1(lackstheDELLAdomain,domainI,inpurple),mutantD8-
2023(lackstheTVHYNPSdomain,domainII,inorange),andwheatmutantRht-B1blacksdomainI(seealsoPengetal.,1999a).
alleleconferspartialresistancetothedwarfingeffectsoftheGA opposableplantgrowthinhibitors.Forexample,thelackofsuch
biosynthesisinhibitorpaclobutrazol(PAC;Pengetal.,1997),a inhibitors would be predicted to suppress the GA-deficient
characteristicpropertyofslenderalleles(e.g.,Pottsetal.,1985). mutantphenotypeofga1-3.Accordingly,lackofGAIandRGA
Thus, lack of GAI (in gai-t6) causes PAC resistance (slender suppressesthedwarfedshootphenotypenormallyconferredby
phenotype), while lack of the DELLA domain (in gai) causes a ga1-3(DillandSun,2001;Kingetal.,2001),lackofRGL2permits
constitutively active mutant growth inhibitor (gai) whose geneti- GA-independent germination of ga1-3 seed (Lee et al., 2002;
callydominantactioncannolongerbeopposedbyGA(Figure2A). Tyleretal.,2004),whilelackofRGA,RGL1,andRGL2permits
ArabidopsisRGAwasidentifiedbyloss-of-functionmutations normalstamenandpetalgrowthinga1-3flowers(Chengetal.,
conferringpartialsuppressionofthega1-3phenotype(achar- 2004; Tyler et al., 2004). In effect, progressive reduction of
acteristic property of slender alleles; Silverstone et al., 1997) DELLAfunctiontendstowardcompletesuppressionofallvisible
and shown to encode a protein (RGA) closely related to GAI GA-deficientphenotypesexhibitedbyga1-3(Chengetal.,2004;
(Silverstoneetal.,1998).Subsequently,itbecameclearthatthe Tyleretal.,2004).Inaddition,theArabidopsisDELLAsdisplay
Arabidopsis genome contains three further GAI/RGA-related both overlapping (e.g., GAI and RGA in stem elongation) and
genes: RGL1, RGL2, and RGL3 (e.g., Lee et al., 2002). The relativelydiscrete(e.g.,RGL2inseedgermination)GAresponse
geneproductsGAI,RGA,RGL1,RGL2,andRGL3comprisethe regulationfunctions.ThecorrespondencebetweenDELLAsand
fullArabidopsiscomplementofwhatarenowknowncollectively theinferredGA-opposablegrowthinhibitorwasconfirmedbythe
astheDELLAs. demonstrationthatslendermutantsinspeciesotherthanArabi-
Thesefindings,togetherwithfurtheranalysis,confirmedthat dopsis carry loss-of-function mutations in GAI/RGA orthologs
theDELLAsareindeedthepreviouslyinferredendogenousGA- (e.g.,Ikedaetal.,2001;Chandleretal.,2002)andthatLaandCry,
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mutantallelesofwhichconferthepeaslenderphenotypeupon
whichtheoriginalinhibitorofaninhibitorhypothesiswasbased
(Brian, 1957), correspond to DELLA-encoding genes (Weston
etal.,2008).
ThemolecularcharacterizationoftheArabidopsisgaimutation
highlighted the importance of the DELLA domain (Figure 2A;
Peng etal.,1997). Thisimportance was further emphasized in
studiesoftheGAinsensitivityofdwarfingmutantsofmaize(D8-1;
D8-2023)andwheat(Rht-B1b).Aswithgai,theGAinsensitivityof
thesemutantsisconferredbymutantDELLAsthatlackfunctional
conserved N-terminal domains, termed DELLA (domain I) or
TVHYNPS (domain II) (Figure 2B; Peng et al., 1999a). Further
studiesidentifieddomainIordomainIImutationsinGA-insensitive
barley(Hordeumvulgare)andrice(Oryzasativa)mutants(Chandler
etal., 2002; Asanoetal., 2009). Inaddition,deletionofdomain
I of Arabidopsis RGA (as conferred by the rga-D17 transgene)
results in a mutant RGA protein (rga-D17) that, similarly to gai,
confers GA-insensitive dwarfism (Dill et al., 2001). Thus, in a
generalsense,mutationofdomainIorIIofDELLAscanprevent
GA opposability and confers GA-insensitive dwarfism. We will
returntothebiologicalfunctionsofdomainsIandIIlaterinthis
review.
The wheat Rht-B1b (and Rht-D1b) alleles are important in
modernagriculture,inthattheyconfertheincreasedgrainyields
of the green revolution varieties containing them (Peng et al.,
1999a). In attempts to further expand the agricultural utility of
domainImutantDELLAs,theArabidopsisgaigenewasshownto
confer dwarfism when expressed in basmati rice (Peng et al.,
1999a; Fu et al., 2001), and a switchable form of gai was
developed thatcanbeusedtoinducegrowthrestraint flexibly
asandwhenrequired(Ait-alietal.,2003). Figure 3. GA Promotes the Proteasome-Dependent Destruction of
Insummary,wild-typeDELLAswereidentifiedasGA-opposable DELLAs.
plant growth inhibitors that can be specifically mutated (in (A)GAtreatmentcausesdisappearanceofGFP-RGAfromArabidopsis
domainsIand/orII)tobecomegrowthinhibitorsthatareresistant root cell nuclei. Right, GA-treated (4 h) pRGA:GFP-RGA roots; left,
to the effects of GA. However, the mechanism via which GA control(seealsoSilverstoneetal.,2001).
overcomesthegrowthinhibitoryeffectsofwild-typeDELLAswas (B)SchematicrepresentationoftheDELLA-SCFSLY1/GID2interaction.The
unknown. DELLA protein (blue) inhibits growth. GA stimulates an interaction
between the DELLA protein and the E3 ubiquitin ligase SCFSLY1/GID2,
resulting inpolyubiquitination of DELLA. Polyubiquitination targets the
DELLAproteinfordestructionbytheproteasome.
GAPROMOTESPROTEASOME-DEPENDENT
DESTRUCTIONOFDELLAs
HowthendoesGAcausethedisappearanceofDELLAs?One
Thestagewasnowsetforin-depthmolecularanalysesofhow possibility was that DELLAs are destroyed by the proteasome
GAovercomesthegrowthinhibitingeffectsoftheDELLAs.The (Sullivanetal.,2003).Initialexperimentsshowedthatthespecific
first breakthrough came from studies of DELLAs fused to the proteasome inhibitor MG132 inhibits the GA-promoted disap-
green fluorescent protein (GFP), in particular GFP-RGA. GFP- pearanceofthebarleyDELLASLN1(Fuetal.,2002).Targetingof
RGAwasshowntoaccumulateinrootcellnucleiandtodisap- proteins to the proteasome occurs via polyubiquitination: the
pear from those nuclei within a few hours of GA treatment attachmentofapolymericchainconsistingofubiquitinprotein
(Silverstoneetal.,2001;Figure3A).Furtherstudiesshowedthat residues.PolyubiquitinationisachievedbyE3ubiquitinligases,
GAcausesdisappearanceofcerealDELLAs(e.g.,barleySLN1 amongwhichistheso-calledSCFcomplexclass(Sullivanetal.,
and rice SLR1; Gubler et al., 2002; Itoh et al., 2002). These 2003).ItistheF-boxproteincomponentoftheSCFcomplexthat
observationssuggestthatGAovercomesthegrowthinhibitory provides specificity, with each F-box protein having specific
effects of DELLAs by promoting their disappearance. Intrigu- affinityforaparticularsetoftargetproteins.Interactionbetween
ingly, GA does not promote the disappearance of DELLA pro- SCF and the target protein promotes polyubiquitination and
teins lacking domain I (Dill et al., 2001; Fu et al., 2004), thus subsequent destruction of the target by the proteasome. Mo-
showing that these mutant proteins, whose growth-inhibiting leculargeneticanalysisofGA-insensitivedwarfmutantsidenti-
propertiesareresistanttoGA,arealsoresistanttoGA-promoted fiedanF-boxprotein(riceGID2/ArabidopsisSLY1)thatispartof
disappearance. a DELLA-interacting E3 ubiquitin ligase that interacts with a
GrowthRegulationbyGA-GID1-DELLA 5of12
C-terminal region oftheDELLA protein(McGinnisetal.,2003; ing,resultingintightspecificityoffitofbioactiveGAwithinthe
Sasaki et al., 2003; Dill et al., 2004; Fu et al., 2004) and that pocket.Forexample,theC3-hydroxylgroup(Figure1A),whichis
targetsDELLAsfordestructionbytheproteasome(Figure3B). essential for GA activity, is hydrogen bonded to a specific Tyr
Thesediscoveriesenabledamolecularunderstandingofhow residueintheinternalsurfaceoftheGID1pocketviaabridging
GAovercomesDELLAfunctionandhencepromotesgrowth:the water molecule (Murase et al., 2008; Shimada et al., 2008).
growth-inhibiting DELLAs are targeted for destruction by the Conversely,additionofa2-hydroxylgroup,aninplantamech-
proteasomeinresponsetoGAfollowingpolyubiquitinationbya anism for the inactivation of bioactive GAs in angiosperms
specificE3ubiquitinligaseoftheSCFclass(SCFSLY1/GID2),thus (Yamaguchi, 2008), is predicted to cause steric interference
relieving DELLA-mediated growth inhibition. Nevertheless, the andconformationalchangesthatwillnotfavorreceptorbinding
questionofhowGApromotestheDELLA-SCFSLY1/GID2interac- (Muraseetal.,2008).
tion remained, and it was only with the discovery of the GA Binding of GA causes an allosteric change to GID1, which
receptorthatitbecameclearhowthisoccurs. resultsintheNterminusformingalidtothepocket(Muraseetal.,
2008; Shimada et al., 2008). Once in place, the upper surface
of the lid binds with the DELLA protein, specifically with the
N-terminal region defined by domains I and II (Murase et al.,
THEGARECEPTORINTERACTSWITHDOMAINSIANDII
2008).TheformationoftheGA-GID1-DELLAcomplexisthought
OFTHEDELLAPROTEIN
toinduceaconformationalchangeinaC-terminaldomainofthe
ThediscoveryoftheGAreceptor(Ueguchi-Tanakaetal.,2005) DELLA protein that stimulates substrate recognition by the
wasamajoradvanceinunderstandingoftheGA-GID1-DELLA SCFSLY1/GID2 E3 ubiquitin ligase, proteasomic destruction of
mechanism. A rice gene (GID1) initially identified by loss-of- DELLA,andtheconsequentpromotionofgrowth.
function gid1 alleles (conferring GA-insensitive dwarfism) was IntriguingrecentevidencesuggeststhatovercomingDELLA-
showntoencodeanuclearGAreceptorprotein(GID1;Ueguchi- mediated growth inhibition does not equate solely with the
Tanakaetal.,2005).GID1islocalized(atleastpredominantly)in destructionofDELLA.Experimentsusingmutantplantslacking
thenucleusandactsthereasasolubleGAreceptor,havinghigh the F-box component of the SCFSLY1/GID2 E3 ubiquitin ligase
affinity for bioactive GAs and low or nonexistent affinity for have indicated that the GA-dependent formation of the GID1-
inactiveGAs.Remarkably,GID1bindsspecificallywiththerice DELLA complex itself (independently of subsequent protein
DELLASLR1whenbothproteinsareexpressedinyeastinthe destruction) reduces the growth-repressing effects of the
presenceofbioactiveGA.UnlikethecaseinArabidopsis,whose DELLAs (Ariizumi et al., 2008; Ueguchi-Tanaka et al., 2008).
genome encodes multiple DELLAs, SLR1 is the sole DELLA Given that DELLAs inhibit growth by interacting with specific
proteinencodedbythericegenome.Accordingly,lackofSLR1 growth-promoting transcription factors (see below), it is likely
(in a slr1-1 loss-of-function mutant) suppresses the dwarfism that formation of the GID1-DELLA complex reduces the avail-
conferredbyagid1loss-of-functionallele,andSLR1accumu- abilityofDELLAsforinteractionwiththosetranscriptionfactors,
latesinthegid1-1loss-of-functionmutant.Takentogether,these thusreducingthe resultantgrowthinhibitory effects.Thus, the
observationssuggestedthatGApotentiatesaninplantainter- GA-stimulated GID1–DELLA interaction inherently reduces
actionbetweentheGID1GAreceptorandDELLAsandthatthis DELLA-mediated growth repression as well as stimulating
interactionstimulatestheGA-dependentdestructionofDELLAs, DELLAdestruction.
thuspromotinggrowth(Ueguchi-Tanakaetal.,2005).
Genes encoding multiple GID1-related GA receptors were
discoveredinArabidopsis,andmutantsmultiplyhomozygousfor
HOWDELLAsINHIBITPLANTGROWTH
loss-of-functionmutationsinthesegeneswereshowntoexhibit
GA-insensitivedwarfism(Griffithsetal.,2006;Iuchietal.,2007; Theaboveadvancesdefinethemolecularmechanismviawhich
Willige et al., 2007). Further analysis showed that the GID1– GAopposesthegrowthinhibitorypropertiesoftheDELLAs,but
DELLAinteractionspecificallyinvolvestheconservedN-terminal they do not explain how DELLAs inhibit growth. Because the
domainsIandIIoftheDELLAprotein(Pengetal.,1999a;Griffiths C-terminaldomainofDELLAsiscloselyrelatedtothatofSCR
et al., 2006; Ueguchi-Tanaka et al., 2007; Willige et al., 2007; andothertranscriptionalregulators,itseemedpossiblethatthe
Feng et al., 2008), thus finally explaining why mutant DELLA DELLAsassociatewithDNA.However,therearenoreportsof
proteinslackingthesedomainsconferGAinsensitivity.Inaddi- directDELLA–DNAassociations.Inaddition,themoderatede-
tion, the GA-stimulated interaction between GID1 and DELLA greeofpromoterenrichmentobtainedinchromatinimmunopre-
itself increases the affinity of DELLA for the SCFSLY1/GID2 E3 cipitation studies (Zentella et al., 2007) suggested that the
ubiquitin ligase (Griffiths et al., 2006), presumably causing in- associationofRGAwithgenepromotersmightinvolveadditional
creasedpolyubiquitinationofDELLA,subsequentdestructionof transcriptionalregulators.
DELLAbytheproteasome,andthepromotionofgrowth. Further advances in understanding of how DELLAs inhibit
Recent crystal structure studies have deepened our under- growthhavecomefromstudiesofplantlightresponses.Plant
standing of the molecular spatial relationships governing the growth is strongly influenced by the light environment. For
interactions between GID1, GA, and DELLA. Essentially, the example, the growth of the Arabidopsis seedling hypocotyl
GID1 protein possesses a central pocket that accommodates (expansionoftheembryonicstemduringseedgerminationand
bioactiveGA.PolargroupsinthebioactiveGAmoleculeinteract seedlingestablishment)isinhibitedbylight.Anumberofstudies
directlywithGID1andwithwatermoleculesviahydrogenbond- had previously implicated GA regulation as a component of
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light-mediated hypocotyl growth regulation (e.g., Peng and growthinhibitorsthatact(atleastinpart)byinterferingwiththe
Harberd,1997),butitisonlyrecentlythattheDELLAshavebeen activity of growth-promoting transcription factors. In addition,
showntocontributetothisprocess.Forexample,DELLA-deficient thegrowthinhibitorypropertiesofDELLAsmaybeenhancedby
Arabidopsis seedling hypocotyl growth is partially insensitive to O-GlcNAcmodificationduetoSPY.(2)GAbindswithintheGA
light-mediatedgrowthinhibition(Achardetal.,2007a),andDELLA bindingpocketoftheGID1GAreceptor,causingthefoldingofa
deficiency also compromises the shade avoidance response lidstructuretowhichtheN-terminalregionoftheDELLAsbinds.
(whereby plants sense and respond to competing neighbors; (3) The GA-GID1-DELLA interaction reduces the growth-
Djakovic-Petrovic et al., 2007). Thus, DELLA-mediated growth repressingeffectofDELLAs,perhapsbyreducingtheircapacity
inhibitionisacomponentoflight-mediatedgrowthinhibition. forinteractingwithgrowth-promotingtranscriptionfactors.(4)The
Thelightsignalsthatelicithypocotylgrowthregulationarefirst GA-GID1-DELLAinteractionalsostimulatesthebindingofDELLA
perceivedbyphotoreceptorsandsubsequentlycommunicated to the SCFSLY1/GID2 E3 ubiquitin ligase. (5) Polyubiquitination of
to signal-transducing transcription factors, such as PHYTO- DELLA by SCFSLY1/GID2 targets DELLA for destruction by the
CHROME INTERACTING FACTOR3 (PIF3) and PIF4. Recent proteasome,thusfinallyremovingtheagentofDELLA-mediated
studies identified a physical interaction between a conserved growthinhibition(Figure4).
Leu-heptad repeat in the DELLAs and the DNA recognition TheGA-GID1-DELLAgrowthregulatorymechanismthussum-
domain of the PIF factors (de Lucas et al., 2008; Feng et al., marizedoperatesinangiospermsandappearstobearelatively
2008). This interaction inhibits the binding of PIF4 to gene recent innovation in plant evolution, having arisen sometime
promotertargetrecognitionsequences(deLucasetal.,2008), betweenthedivergencesofthebryophytesandthelycophytes
suggesting that DELLAs restrain growth by sequestering PIFs fromthelandplantlineage(Hiranoetal.,2007;Yasumuraetal.,
into inactive protein complexes, thus inhibiting their ability to 2007).ThemostprominentfunctionoftheangiospermGA-GID1-
promote growth via gene transcriptional activation. These ob- DELLAmechanismisregulationofthegrowthoforgansfollowing
servationsprovideapossiblegeneralframeworkforunderstand- theirdefinitioninshootandrootapicalmeristems.Forexample,
ing how DELLAs inhibit plant growth. According to this the Arabidopsis ga1-3 mutant has both a dwarfed shoot
framework,DELLAsinhibitgrowthbyinterferingwiththeactivity (Richardsetal.,2001)andashortroot(FuandHarberd,2003),
ofgrowth-promotingtranscriptionfactors. inpartbecauseGAregulatespostmeristematicgrowthofthese
organs.Infact,theGA-GID1-DELLAmechanismplaysamajor
roleintheregulationoforganextensiongrowthofshootandroot
ALTERNATIVE(NON-GA)ROUTESTODELLA-DEPENDENT and does so via interaction with the auxin signaling pathway:
GROWTHCONTROL auxinregulatesgrowth(atleastinpart)bythemodulationofboth
GAbiosynthesisandGAresponsiveness(Rossetal.,2000;Fu
Theabovedescribedadvancesprovideamolecularframework
and Harberd,2003).Recentevidence indicates thatGA-GID1-
forunderstandinghowGAquantitativelyregulatesplantgrowth.
DELLA regulation of root extension growth is not generally
However, it is becoming clear that there are additional, GA-
distributedthroughoutrootcelllayers,butoperatesprimarilyin
independent factors that can modulate the growth inhibitory
theendodermis(Ubeda-Toma´setal.,2008).
function of the DELLAs. One such factor is the putative
Inadditiontoitsmajorroleinmodulatingextensiongrowthof
O-GlcNAc transferase encoded by SPY (reviewed in Richards
plantorganssubsequenttotheirdefinitioninapicalmeristems,
etal.,2001).Loss-of-functionspyallelespartiallysuppressthe
theGA-GID1-DELLAmechanismalsodeterminessomeaspects
dwarfphenotypesconferredbyga1-3,gai,andrga-D17(Peng
of developmental patterning. For example, maintenance of
et al., 1997, 1999b; Silverstone et al., 1997, 2007). O-GlcNAc
pluripotencyinthecellsofthevegetativeshootapicalmeristem
transferasestypicallycatalyzeO-GlcNAcmodificationoftarget
(the group of cells from which arise the aerial parts of angio-
Serresiduesinregulatoryproteins.AreductioninSPYactivity
sperms)isinpartdependentondampeningofGA-GID1-DELLA
(e.g.,asconferredbyspyalleles)causesanincreaseinDELLA
signaling mediated by KNOX transcription factors (Hay et al.,
proteinabundance(asdetectedantigenicallyorviaGFP-DELLA
2002; Jasinskiet al.,2005). Conversely,growing (postmeriste-
fusion),ratherthanthereductionthatmightapriorihavebeen
matic)cellscharacteristicallyhaveactivatedGAsignaling.
expected for a mutation that causes a reduction in DELLA-
mediated growth inhibition (Shimada et al., 2006; Silverstone
etal.,2007).Oneplausibleexplanationfortheseobservations(as
yet unverified) is that O-GlcNAc modification of DELLAs acti- THEGA-GID1-DELLAMECHANISMENABLESAFLEXIBLE
vates (or enhances) the growth inhibition function of DELLAs. GROWTHREGULATIONRESPONSETO
Modulation ofO-GlcNAc transferaseactivityvia environmental ENVIRONMENTALVARIABILITY
or developmental variables thus provides a potential non-GA
PossiblereasonswhyangiospermsmighthaveevolvedtheGA-
routeforgrowthcontrolviamodulationofDELLAactivity.
GID1-DELLA mechanism of growth regulation become clear
when one considers the plant life strategy. Plants are sessile
organismsthatneedtobeabletorespondappropriatelyandin
THEGA-GID1-DELLAPLANTGROWTH
situtothebioticandabioticenvironmentalchallengeswithwhich
REGULATORYMECHANISM
theyarefaced.Thereisaparticularneedtoregulategrowthin
Theadvancesinunderstandingoutlinedintheprecedingpara- responsetoenvironmentalvariability,inpartbecausegrowthis
graphscanbesummarizedasfollows(Figure4):(1)DELLAsare energetically demanding and in part because growth-driven
GrowthRegulationbyGA-GID1-DELLA 7of12
Figure4. TheGA-GID1-DELLAMechanismofAngiospermGrowthRegulation.
Forstep-by-stepguidetopoints(1)to(5)inthemechanism,seemaintext.Growthresultsfromactivationofgrowth-promotinggenes(geneactivated).
FormationoftheGA-GID1-DELLAcomplexfreestranscriptionfactorsfromsequestrationbyDELLAs,enablingpreviouslyinactivegrowth-promoting
genestobecomeactivated.
increasesinbodyvolume/surfaceareatendtoincreasevulner- correlation between ethylene-mediated growth inhibition and
ability. Recentstudies show that the GA-GID1-DELLA mecha- DELLAaccumulation.Theconclusionfromthesestudiesisthat
nism is highly integrated within the overall angiosperm ethyleneinhibitsgrowth(atleastinpart)viaaDELLA-dependent
informationalsignalingandresponsesystem.Wehavealready mechanism.However,therearecircumstancesinwhichethyl-
touched upon the relationship between GA-GID1-DELLA and ene promotes (rather than inhibits) the growth of light-grown
light signaling in growth regulation. Additional examples come hypocotyls, and in this case, promotion interestingly is also
from studiesof the relationship between GA-GID1-DELLA, the accompanied by an accumulation (rather than a depletion) of
phytohormoneethylene,andplantstressresponses.Ageneral GFP-RGA in hypocotyl nuclei (Vandenbussche et al., 2007). It
idea emerging from these studies is that the GA-GID1-DELLA seemsthatinthiscaseethylenestillpromotesGFP-RGAaccu-
mechanism enables plants to maintain transient growth arrest mulation, but this accumulation is not translated into growth
andthustosurviveperiodsofadversity. inhibition. Thus, the frequently observed negative correlation
EthyleneisperceivedbytheETR1familyofethylenereceptors, between growthand DELLA accumulation is not absolute and
thuscausinginactivationofCTR1(aRafkinase–relatedrepres- canbebrokeninspecificcircumstances.Asdescribedabovein
sorofethylenesignaling)andresultantaccumulationofEIN3and thecaseofthespymutantphenotype,theseobservationsare
EIN3-like ethylene-signaling transcription factors (Guo and indicativeofaphysiologicalroleforregulationofinherentgrowth
Ecker, 2004). Initial investigations of the relationship between inhibitory activity of DELLAs that is independent of DELLA
ethylenesignalingandtheGA-GID1-DELLAmechanismshowed accumulation.
thatethyleneinhibitsDELLA-deficientmutantArabidopsisseed- The close relationships between ethylene signaling and the
lingrootgrowthlessthanthatofthewildtypeandthatethylene GA-GID1-DELLA mechanism continue through stages of the
inhibitstheGA-induceddisappearanceofGFP-RGAviaCTR1- plantlifecyclebeyondseedlingemergence.Forexample,recent
dependentsignaling(Achardetal.,2003).Inaddition,themain- studiesshowthatethyleneregulatesthetransitionfromvegeta-
tenance of the exaggerated apical hook structure typical of tive to reproductive growth, and does so, at least in part, via
dark-grownethylene-treatedseedlingswasshowntobedepen- interactionwiththeGA-GID1-DELLAmechanism.Theactivation
dentonlossofDELLA-mediatedgrowthinhibition(Achardetal., ofethylenesignalingresultsinareductioninGAlevels,andthis
2003;Vriezenetal.,2004).Thus,thereisaconnectionbetween delays floral induction via a DELLA-dependent mechanism. In
ethyleneresponseandtheGA-GID1-DELLAmechanismanda addition, a lack of DELLAs suppresses the delayed flowering
8of12 ThePlantCell
characteristic of the constitutive ethylene response phenotype resulting in reduced carbohydrate consumption and inhibited
conferredbyctr1loss-of-functionalleles(Achardetal.,2007b). growthinresponsetofloodinginrice(FukaoandBailey-Serres,
Further analysis indicates that ethylene likely affects DELLAs 2008),justasDELLAsinhibitgrowthinresponsetosaltstressin
downstream of the EIN3 transcriptional regulator and delays Arabidopsis (Achard et al., 2006). These observations suggest
flowering by repressing the activity of floral meristem identity thattheGA-GID1-DELLAmechanismprovidesageneralmech-
genes (LEAFY and SUPPRESSOR OF OVEREXPRESSION OF anism for inhibition of growth and associated resource con-
CONSTANS1;Achardetal.,2007b).Theseobservationsidentify sumptioninresponsetoenvironmentaladversity.
the GA-GID1-DELLA mechanism as a previously unknown ThelikelihoodthattheGA-GID1-DELLAmechanismisindeed
bridgebetweentheethylenesignalingpathwayandfloralmer- a general mechanism for modulating growth response to the
istemidentitygenesintheregulationofthetransitionbetween environmentisincreasedbyrecentdiscoveriesthatitregulates
vegetativetoreproductivegrowth,probablyprovidingamech- growthinresponsetochangeinawidevarietyofenvironmental
anismviawhichenvironmentalstressregulatesthattransition. variables.Forexample,theeffectsofcoldtemperaturesonplant
SeveralstudieshavedirectlyimplicatedtheGA-GID1-DELLA growth signaled by the cold-induced CBF1 factor-dependent
mechanisminregulatingtheresponseofplantstoenvironmental pathwayaremediatedviaeffectsonGAmetabolism(andcon-
stress. For example, high salinity slows the growth of plants. sequently on DELLAs; Achard et al., 2008b), and growth and
StudieswithDELLA-deficientArabidopsismutantsshowedthat developmental responses to phosphate starvation are also
saltslowsgrowthviaapartiallyDELLA-dependentmechanism modulatedbytheGA-GID1-DELLApathway(Jiangetal.,2007).
(Achardetal.,2006).Furtherstudiesrevealedthatsaltcausesa An unexpected recent development has been the discovery
reductionininplantabioactiveGAlevels(Achardetal.,2006)and thattheGA-GID1-DELLAmechanismplaysaroleintheregula-
thatthisreductioncanbeexplained,atleastinpart,byactivation tion of plant–pathogen interactions. Studies of the pathogen
of genes encoding GA-2oxidase, an enzyme that deactivates responses of DELLA-deficient Arabidopsis plants showed that
bioactiveGAsbyadditionofahydroxylgrouptothe2Cposition DELLAaccumulationdifferentially affectsresponsetodifferent
(Figure1A;Magomeetal.,2008).Thus,saltinhibitsplantgrowth classes of pathogen. Thus, presence of DELLAs is associated
by reducing bioactive GA abundance, in turn causing accu- with susceptibility to virulent biotrophs and with resistance to
mulation of DELLAs and consequent growth inhibition. Salt- necrotrophs,propertiesthatarerelatedtoaneffectoftheGA-
activated DELLA-dependent growth inhibition presumably has GID1-DELLA pathway on the balance between jasmonic acid
adaptivesignificancebecauseplantslackingDELLAsaremore and salicylic acid signaling (Navarro et al., 2008). Although
susceptible,whereasplantsinwhichDELLAsaccumulate(e.g., concordant with previous examples of the GA-GID1-DELLA
ga1-3) are more resistant to the lethal effects of extreme salt mechanism acting as a mediating bridge between different
(Achardetal.,2006).TheseobservationsindicatethattheGA- signaling pathways, these observations were unexpected be-
GID1-DELLAmechanismprovidesplantswithameansofreg- causetheyrepresentidentificationofaGA-GID1-DELLA–regu-
ulatinggrowthappropriatetoenvironmentalconditions,enabling lated phenomenon that is not strictly growth related (the
aslowingofgrowthandreducedenergeticcommitmentduring pathogenicity assays usedin theseexperiments involved rela-
periodsofenvironmentaladversity.Achardetal.(2008a)iden- tivelymatureleavesthatwerenolongerinthegrowingphase).It
tifiedareductioninreactiveoxygenspecieslevelsasapossible ispossiblethatthereareadditionalnon-growthaspectsofGA-
mechanism for the restraint of growth and the concomitant GID1-DELLAbiologythatareyettobediscovered.
promotionofsurvivalofadversesalinity.
AlinkbetweenethyleneandtheGA-GID1-DELLAmechanism
has also been implicated in the growth responses of rice to
DOESTHEGA-GID1-DELLAMECHANISMHAVE
flooding. Flood-tolerant rice survives temporary submergence
ADAPTIVESIGNIFICANCE?
viaatransientinhibitionofgrowthandcarbohydrateconsump-
tionthatiscontrolledbyanethylene-responsivefactorERF-type GiventhattheGA-GID1-DELLAmechanismplayssuchaprom-
transcriptionfactorencodedbytheSub1Agene.Submergence inentroleintheresponseofplantstoenvironmentalvariables,it
causes ethylene production and the consequent activation of mightbeexpectedthatpossessionofthismechanismisselec-
Sub1A. In turn, Sub1A inhibits elongation growth by causing tively advantageous and that variant forms of it might have
increasedaccumulationofthericeDELLASLR1andofarelated adaptive significance. Recent studies monitored the effects of
protein, SLRL1 (Fukao and Bailey-Serres, 2008). SLRL1 is a artificial selection on anexperimental wheat population segre-
proteinthatinhibitsgrowthbutlacksfunctionaldomainsIandII gatingforRht-B1aandRht-B1b(wheatDELLA-encodingalleles
(seeabove)andthusinhibitsgrowthinaGA-resistantfashion. conferring tall and dwarf plant phenotypes, respectively; Peng
Therefore,SLRL1isfunctionallyanalogoustothemutantDELLA etal.,1999a;Raquinetal.,2008).Meanplantheightincreased
proteins encoded bythe mutant gai, D8-1, D8-2023, and Rht- steadilywithnumberofgenerationspostthefounderpopulation
B1b alleles described above and is a protein that rice has generation, as did the relative frequency of the RhtB1a allele,
recruited to function in flooding response. Thus, as shown indicating that Rht-B1a was under strong positive selection
previously in Arabidopsis (Achard et al., 2003), ethylene can throughoutthe17generationsoftheexperiment(Raquinetal.,
inhibitricegrowthusingaGA-GID1-DELLA–dependentmecha- 2008). At first sight this may seem paradoxical given the well-
nism(viaSLR1)andadditionallyusingaDELLA-relatednon-GA documentedincreasesingrainyieldconferredbyRht-B1b(see
opposablegrowthinhibitoryprotein(SLRL1).ActivationofSLR1 above),theveryincreasesthatwereresponsiblefortheuseof
andSLRL1bySub1Asuppressesenergy-consumingprocesses, theRht-B1balleleingreenrevolutionwheatvarieties.However,
GrowthRegulationbyGA-GID1-DELLA 9of12
tallerplantspresumablycompetemoreeffectivelyforlightand limitingfactorinplantgrowthregulation,anddifferentialregula-
nutrientswhengrowninheterogeneouspopulations(asopposed tion of SLY1 expression is potentially a mechanism via which
tothehomogeneouspopulationstypicalofmodernwheatfields). different plant signaling pathways may (independently of GA)
Inaddition,thestrengthofselectionagainstRht-B1bindicates regulate plant growth by reducing DELLA-mediated growth
thatallelesconferringDELLAsresistanttooppositionbyGAwill inhibition. Future studies will determine the contributions of
beatacompetitivedisadvantageinmanynaturalenvironments, these (and other) non-GA routes to the modulation of DELLA
perhapsbecausetheimpairedGAopposabilityimposesaclamp growthinhibitoryfunction.
on the flexibility with which plants can modulate growth in Anotherlikelyimportantareaoffutureinvestigationconcerns
responsetoenvironmentalchange. theroleofDELLAsasintegratorsofgrowthresponsestoavariety
of signals. It has been suggested that the GA-GID1-DELLA
mechanismisnodalandprovidesamechanismforintegrating
multiple input signals into a single growth output (Alvey and
THEGA-GID1-DELLAMECHANISM:OUTSTANDING
Harberd,2005).However,manyquestionsremain,notleastwith
ISSUESANDQUESTIONS
respecttotheunravelingoftherelativeextentstowhichother
Asreviewedabove,recentresearchhasshownthattheDELLAs signals (including other hormones) impact upon GA-GID1-
are the GA-opposable endogenous plant growth inhibitors DELLAactivitythroughregulationofbioactiveGAbiosynthesis
whose existence was first postulated in the late 1950s. We and inactivation, regulation of DELLA susceptibility to GA-
havesummarizedthemolecularnatureoftheGA-GID1-DELLA mediatedoppositionofDELLAactivity(interactionwiththeGA
mechanism,themechanismviawhichplantsrespondtoGA,and receptor and/or subsequent degradation), or modulation of
argued that this mechanism enables plasticity of growth in DELLAactivitybyothermeans.Furthermore,itisclearthatthe
responsetoenvironmentalvariability.Wenowpointoutanum- GA-GID1-DELLA mechanism is not the sole mechanism for
ber of outstanding issues and questions that are likely fertile integration of growth regulation. For example, DELLAs inhibit
areasforfutureresearch. hypocotyl growth in response to light, but a DELLA-deficient
First, as described above, the recent demonstration that hypocotylisstillpartiallyphotomorphogenetic(islongerthanthe
DELLAsinteractwithPIF3/PIF4transcriptionfactorsprovidesa wild type in light but not as long as a dark-grown wild-type
potential general model for understanding how DELLAs inhibit hypocotyl;Achardetal.,2007a;Fengetal.,2008).Thus,there
growth. However, the degree of specificity of this interaction mustbeadditionalresponseintegratorsthatworkinconjunction
remainsunclear.ThePIFsareasubsetofthebasichelix-loop- withtheDELLAstoinhibithypocotylgrowthinresponsetolight.
helix (bHLH) family of transcription factors. Perhaps DELLAs Byextension,itislikelythatthereareadditionalintegratorsthat
interactwithawiderspectrumofbHLHsthanthosedefinedas coordinatetheregulationofgrowthinresponsetoenvironmental
PIFs, thus sequestering various bHLHs away from the gene variablesingeneral,anddeterminingtheirrelationshipwiththe
promotersthattheyactivate.Suchascenariomightexplain,at DELLAsisanimportanttaskforthefuture.
leastinpart,thepervasiverolesthatDELLAsappeartoplayin An additional emerging idea concerns the possible relation-
angiosperm biology. In addition, since the bHLH transcription ship between DELLA-mediated growth inhibition and resource
factorPIL5regulatestheexpressionofDELLA-encodinggenes allocation. Essentially, growth inhibition might have adaptive
(Ohetal.,2007),itispossiblethatDELLAsfeedbackregulatetheir significance when environmental impacts (both biotic and abi-
ownexpressionviainteractionwithbHLHtranscriptionfactors. otic)threatenresourcelimitation.Prioritizationofresourceallo-
Second,thisreviewhasshownhowGAregulatesthegrowth cationmayresultinresourcesbeingdivertedawayfromgrowth
inhibition function of DELLAs. However, there are increasing in favor of defense against pathogens or in the adoption of a
indicationsthatDELLAfunctioncanalsobemodifiedviaroutes strategy that involves reduced resource consumption during a
thatdonotdirectlyinvolveGA.Amongthesepossibleroutesare periodofwaitforimprovedenvironmentalconditions.Thus,the
transcriptional regulation of genes encoding DELLAs (e.g., Oh GA-GID1-DELLAmechanismmayenabletherobustadaptation
et al., 2007; Fukao and Bailey-Serres, 2008), posttranslational of various aspects of angiosperm biology to environmental
activationofDELLAs,andnon-GAroutesformodulatingDELLA threat.
abundance.Onepossiblerouteforposttranslationalactivationof Finally, it is possible that consideration of the meaning of
DELLAsisthelikelyO-GlcNActransferaseactivityencodedby “growth inhibition” at the cellular level will prove fruitful. The
SPY(discussedabove),althoughmodulationofthisactivityhas intriguingpotentialroleofreactiveoxygenspeciesinGA-GID1-
not yet been shown to regulate DELLA activity differentially DELLA–mediatedgrowthregulationisdescribedabove,andthis
in response to physiological or environmental variables. If is likely to be an important area of further investigation. In
O-GlcNAc modification indeed enhances the growth inhibitory addition, plant cell expansion is often characterized as being
properties of DELLAs, it is possible that this modification pro- theproductofopposingforcesof(growth-promoting)intracel-
motes the interaction between DELLAs and PIF3/4 (or other lularturgorpressureandthe(growth-inhibiting)turgor-resisting
bHLHs).Apossiblepointofnon-GAregulationofDELLAabun- forcesofthecellwall.Thisviewhasparallelswiththeproposal
danceistherateofpolyubiquitination(andhencedestruction)of thatgrowthisregulatedbytheopposingforcesofGAandaGA-
DELLAs by the SCFSLY1/GID2 E3 ubiquitin ligase. For example, opposablegrowthinhibitor,theinhibitorofaninhibitorproposal
transgenic overexpression of SLY1 (presumably causing in- with which this review began. Could it be that an increase in
creasedSLY1availability)promotesgrowthbyincreasingDELLA DELLA-mediated inhibition of growth equates ultimately to an
destruction (Fu et al., 2004). Thus, SLY1 availability can be a increaseintheresistanceofthecellwall?
10of12 ThePlantCell
ACKNOWLEDGMENTS for gibberellin-induced degradation of RGA. Proc. Natl. Acad. Sci.
USA98:14162–14167.
WorkinourlaboratoryisfundedbytheUKBiotechnologyandBiological Dill,A., andSun, T.-p.(2001). Synergistic derepression ofgibberellin
SciencesResearchCouncil(responsemodesGrantBB/F020759/1). signalingbyremovingRGAandGAIfunctioninArabidopsisthaliana.
Genetics159:777–785.
Dill,A.,Thomas,S.G.,Hu,J.,Steber,C.M.,andSun,T.-p.(2004).The
ReceivedMarch12,2009;revisedApril30,2009;acceptedMay3,2009; Arabidopsis F-box protein SLEEPY1 targets gibberellin signaling
publishedMay26,2009. repressorsforgibberellin-induceddegradation.PlantCell16:1392–
1405.
Djakovic-Petrovic,T.,deWit,M.,Voesenek,L.A.C.J.,andPierik,R.
REFERENCES (2007). DELLA protein function in growth responses to canopy sig-
nals.PlantJ.51:117–126.
Achard,P.,Baghour,M.,Chapple,A.,Hedden,P.,VanDerStraeten,
Feng,S., etal.(2008).CoordinatedregulationofArabidopsis thaliana
D., Genschik, P., Moritz, T., and Harberd, N.P. (2007b). The plant
developmentbylightandgibberellins.Nature451:475–479.
stresshormoneethylenecontrolsfloraltransitionviaDELLA-dependent
Fu, X., and Harberd, N.P. (2003). Auxin promotes Arabidopsis root
regulationoffloralmeristem-identitygenes.Proc.Natl.Acad.Sci.USA
growthbymodulatinggibberellinresponse.Nature421:740–743.
104:6484–6489.
Fu,X.,Richards,D.E.,Ait-ali,T.,Hynes,L.W.,Ougham,H.,Peng,J.,
Achard, P., Cheng, H., De Grauwe, L., Decat, J., Schoutteten, H.,
andHarberd,N.P.(2002).Gibberellin-mediatedproteasome-dependent
Moritz,T.,VanDerStraeten,D.,Peng,J.,andHarberd,N.P.(2006).
degradationofthebarleyDELLA-proteinSLN1repressor.PlantCell14:
Integrationofplantresponsestoenvironmentallyactivatedphytohor-
3191–3200.
monalsignals.Science311:91–94.
Fu,X.,Richards,D.E.,Fleck,B.,Xie,D.,Burton,N.,andHarberd,
Achard, P., Gong, F., Cheminant, S., Alioua, M., Hedden, P., and
N.P.(2004).TheArabidopsismutantsly1gar2-1proteinpromotesplant
Genschik,P.(2008b).Thecold-inducibleCBF1factor-dependentsig-
growthbyincreasingtheaffinityoftheSCFSLY1E3ubiquitinligasefor
nalingpathway modulates theaccumulation ofthegrowth-repressing
DELLAproteinsubstrates.PlantCell16:1406–1418.
DELLAproteinsviaitseffectongibberellinmetabolism.PlantCell20:
Fu, X., Sudhakar, D., Peng, J., Richards, D.E., Christou, P., and
2117–2129.
Harberd, N.P. (2001). Expression of Arabidopsis GAI in transgenic
Achard, P., Liao, L., Jiang, C., Desnos, T., Bartlett, J., Fu, X., and
rice represses multiple gibberellin responses. Plant Cell 13: 1791–
Harberd,N.P.(2007a).DELLAscontributetoplantphotomorphogen-
1802.
esis.PlantPhysiol.143:1163–1172.
Fukao,T.,andBailey-Serres,J.(2008).Submergencetolerancecon-
Achard,P.,Renou,J.-P.,Berthome´,R.,Harberd,N.P.,andGenschik,
ferred by Sub1A is mediated by SLR1 and SLRL1 restriction of
P. (2008a). Plant DELLAs restrain growth and promote survival of
gibberellinresponsesinrice.Proc.Natl.Acad.Sci.USA105:16814–
adversitybyreducingthelevelsofreactiveoxygenspecies.Curr.Biol.
16819.
18:656–660.
Griffiths,J.,Murase,K.,Rieu,I.,Zentella,R.,Zhang,Z.L.,Powers,
Achard, P., Vriezen, W.H., Van Der Straeten, D., and Harberd,
S.J.,Gong,F.,Phillips,A.L.,Hedden,P.,Sun,T.P.,andThomas,
N.P.(2003).Ethyleneregulates Arabidopsis development viamodu-
S.G. (2006). Geneticcharacterizationandfunctional analysisofthe
lation of DELLA protein growth repressor function. Plant Cell 15:
2816–2825. GID1gibberellinreceptorsinArabidopsis.PlantCell18:3399–3414.
Ait-ali, T., Rands, C., and Harberd, N.P. (2003). Flexible control of Gubler, F., Chandler, P.M., White, R.G., Llewellyn, D.J., and
plantarchitectureandyieldviaswitchableexpressionofArabidopsis Jacobsen,J.V.(2002).Gibberellinsignalinginbarleyaleuronecells.
gai.PlantBiotechnol.J.1:337–343. ControlofSLN1andGAMYBexpression.PlantPhysiol.129:191–200.
Alvey, L., and Harberd, N.P. (2005). DELLA proteins: Integrators of Guo,H.,andEcker,J.R.(2004).Theethylenesignalingpathway:New
multipleplantgrowthregulatoryinputs?Physiol.Plant.123:153–160. insights.Curr.Opin.PlantBiol.7:40–49.
Ariizumi,T.,Murase,K.,Sun,T.-p.,andSteber,C.M.(2008).Proteolysis- Harberd,N.P.,andFreeling,M.(1989).Geneticsofdominantgibberellin-
independentdownregulationofDELLArepressioninArabidopsisbythe insensitivedwarfisminmaize.Genetics121:827–838.
gibberellinreceptorGIBBERELLININSENSITIVEDWARF1.PlantCell20: Hay,A.,Kaur,H.,Phillips,A.,Hedden,P.,Hake,S.,andTsiantis,M.
2447–2459. (2002).ThegibberellinpathwaymediatesKNOTTED1-typehomeobox
Asano, K., Hirano, K., Ueguchi-Tanaka, M., Angeles-Shim, R.B., functioninplantswithdifferentbodyplans.Curr.Biol.12:1557–1565.
Komura,T.,Satoh,H.,Kitano,H.,Matsuoka,M.,andAshikari,M. Hirano, K., et al. (2007). The GID1-mediated gibberellin perception
(2009). Isolation and characterization of dominant dwarf mutants, mechanismisconservedinthelycophyteSelaginellamoellendorfiibut
Slr1-d,inrice.Mol.Genet.Genomics281:223–231. notinthebryophytePhyscomitrellapatens.PlantCell19:3058–3079.
Brian,P.W.(1957).Theeffectsofsomemicrobialmetabolicproductson Ikeda,A.,Ueguchi-Tanaka,M.,Sonoda,Y.,Kitano,H.,Koshioka,M.,
plantgrowth.Symp.Soc.Exp.Biol.11:166–182. Futsuhara, Y., Matsuoka, M., and Yamaguchi, J. (2001). Slender
Chandler, P.M., Marion-Poll, A., Ellis, M., and Gubler, F. (2002). rice, a constitutive gibberellin response mutant, is caused by a null
MutantsattheSlender1locusofbarleycvHimalaya.Molecularand mutationoftheSLR1gene,anorthologoftheheight-regulatinggene
physiologicalcharacterisation.PlantPhysiol.129:181–190. GAI/RGA/RHT/D8.PlantCell13:999–1010.
Cheng,H.,Qin,L.,Lee,S.,Fu,X.,Richards,D.E.,Cao,D.,Luo,D., Itoh,H.,Ueguchi-Tanaka,M.,Sato,Y.,Ashikari,M.,andMatsuoka,
Harberd,N.P.,andPeng,J.(2004).GibberellinregulatesArabidopsis M. (2002). The gibberellin signalling pathway is regulated by the
floraldevelopmentviasuppressionofDELLAproteinfunction.Devel- appearanceanddisappearanceofSLENDERRICE1innuclei.Plant
opment131:1055–1064. Cell14:57–70.
de Lucas, M., Davierre, J.M., Rodriguez-Falcon, M., Pontin, M., Iuchi, S., Suzuki, H., Kim, Y.C., Iuchi, A., Kuromori, T., Ueguchi-
Iglesias-Pedraz,J.M.,Lorrain,S.,Fankhauser,C.,Blazquez,M.A., Tanaka,M.,Asami,T.,Yamaguchi,I.,Matsuoka,M.,Kobayashi,
Titarenko, E., and Prat, S. (2008). A molecular framework for light M.,andNakajima,M.(2007).Multipleloss-of-functionofArabidopsis
andgibberellincontrolofcellelongation.Nature451:480–484. gibberellin receptor AtGID1s completely shuts down a gibberellin
Dill,A.,Jung,H.-S.,andSun,T.-p.(2001).TheDELLAmotifisessential signal.PlantJ.50:958–966.